A Study of RO5212054 (PLX3603) in Participants With BRAF V600-Mutated Advanced Solid Tumors

NCT01143753 | Completed Phase 1

• 2 other identifiers: NP252472010-018330-42
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 5

Brief Summary

This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 \[PLX3603\] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Dose Limiting Toxicity

  Baseline up to 21 days

• Maximal Tolerated Dose of RO5212054

  Baseline up to 21 days

• Maximum Plasma Concentration of RO5212054

  Detailed timeframe: Pre-dose (0 hour \[hr\]): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)

  Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)

• Time to Reach Maximum Plasma Concentration of RO5212054

  Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)

  Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)

• Area Under The Plasma Concentration-Time Curve of RO5212054

  Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)

  Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)

Secondary Outcomes (1)

• Percentage of Participants With Adverse Events

  Baseline up to approximately 7 years

Study Arms (2)

RO5212054: Continuous Dosing Cohort

EXPERIMENTAL

Participants will receive RO5212054 in escalating dose levels.

Drug: RO5212054

RO5212054: New Formulation (F05) Bridging Cohort

EXPERIMENTAL

Participants will receive RO5212054 as a single dose of new formulation (F05-150 mg film-coated tablet with different ratios of ingredients than F03 to increase bioavailability) and a single dose of current clinical Formulation (F03-150 mg film-coated tablet) in a cross-over manner. Participants will be alternately assigned to receive either F05 or F03 as their first dose, followed by the opposite Formulation as their second dose. Dose of RO5212054 will be decided based on the results of continuous dosing cohort.

Drug: RO5212054

Interventions

RO5212054 DRUG

Participants will receive RO5212054 at a starting dose of 200 milligrams (mg) orally once daily in each 21 day cycle. Dose levels for escalation will be decided based on the safety assessment of previous cohort. Dose escalations in increments of 50-100 percent are planned.

Also known as: PLX3603

RO5212054: Continuous Dosing Cohort; RO5212054: New Formulation (F05) Bridging Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced solid tumor
• Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate liver, renal and bone marrow function

You may not qualify if:

• Participants for whom standard therapy exists and is considered appropriate by the investigator
• Prior treatment with an inhibitor of BRAF (sorafenib allowed)
• Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis
• Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug
• Anticipated or ongoing anti-cancer therapies other than those administered in this study
• Serious cardiovascular illness within the 6 months prior to study drug administration

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (5)

Royal Adelaide Hospital; Oncology

Adelaide, South Australia, 5000, Australia

Location

Austin Hospital; Medical Oncology

Heidelberg, Victoria, 3084, Australia

Location

Royal Melbourne Hospital; Hematology and Medical Oncology

Parkville, Victoria, 3052, Australia

Location

Rigshospitalet, Onkologisk Klinik

København Ø, 2100, Denmark

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Related Publications (1)

• Dienstmann R, Lassen U, Cebon J, Desai J, Brown MP, Evers S, Su F, Zhang W, Boisserie F, Lestini B, Schostack K, Meresse V, Tabernero J. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors. Target Oncol. 2016 Apr;11(2):149-56. doi: 10.1007/s11523-015-0381-x.

  PMID: 26310975 DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2010
• First Posted: June 14, 2010
• Study Start: July 27, 2010
• Primary Completion: June 30, 2012
• Study Completion: May 2, 2017
• Last Updated: July 28, 2017

Record last verified: 2017-07

Locations

AU (3); ES (1); DK (1)